• First data from collaboration with Dr Shawn Kwatra and Dr Madan Kwatra show increased IL-13Rα1 expression on mast cells and eosinophils in skin samples from atopic dermatitis (AD) patients, reinforcing central role of IL-13Rα1
• Eblasakimab significantly reduced neuronal itch sensitization caused by distinct IL-4 and IL-13 itch pathways and an emerging role of IL-13Rα1 signaling in mediating neuronal excitability and sensitivity beyond AD was identified

MENLO PARK, Calif. and SINGAPORE, Sept. 28, 2022 (GLOBE NEWSWIRE) -- ASLAN Pharmaceuticals (NASDAQ: ASLN), a clinical-stage, immunology-focused biopharmaceutical company developing innovative treatments to transform the lives of patients, today announced the presentation of new translational eblasakimab data at the 51st Annual European Society for Dermatological Research (ESDR) Meeting. Two posters are being presented as e-posters throughout the duration of the congress from September 28 to October 1, 2022, in Amsterdam, Netherlands.

“The new translational data presented at ESDR provide novel and differentiated mechanistic insights into IL-13Rα1 mediated cytokine signaling in AD. Initial data from our collaboration with Dr Shawn Kwatra and Dr Madan Kwatra showed higher expression of IL-13Rα1 in both mast cells and eosinophils, key drivers of inflammation in AD, within lesional sites of inflamed skin, reinforcing the central role for IL-13Rα1 in driving AD pathology,” said Dr Ferda Cevikbas, Head, Translational Sciences at ASLAN Pharmaceuticals. “Furthermore, changes in gene expression suggests fundamental signaling differences between the Type 1 and Type 2 receptors, and drugs targeting these receptors may have distinct downstream effects leading to different clinical outcomes. The data from the neuronal studies confirm our previous findings that IL-13Rα1 signaling is important for neuronal sensitization to itch pathways through specific itch receptors and shows for the first time that IL-13Rα1 signaling may be critical in mediating neuronal excitability and sensitivity beyond AD. These data support the importance of IL-13Rα1 as a target in AD, providing a potentially differentiated approach for eblasakimab to reduce inflammation and itch in AD patients.”

2022 ESDR e-poster details

Poster 1

Spatial localization and functional role of IL-13Rα1 signalling in atopic dermatitis
(abstract ID: LB060)

Discussion

AD is a chronic inflammatory skin disease that is associated with significant pruritus (itch)¹. It is the most burdensome symptom reported by AD patients. The IL-4/IL-13 receptor system serves as a clinically validated therapeutic target for AD and consists of the Type 1 (IL-14Rα1 and the common γ chain) and Type 2 (composed of IL-4Rα1 and IL-13Rα1) receptors². The poster shows results from an analysis of the expression pattern of IL-13Rα1 in skin derived from AD patients and compared to healthy controls in a study designed to better understand the role of IL-13Rα1 in AD using spatial localization with immunohistochemistry (IHC) and to delineate the function of the Type 1 and 2 receptors using comparative transcriptomics.

Results

The data showed a significant increase of IL-13Rα1 expression in lesional (L) (P<0.001) and non-lesional (NL) (P=0.45) AD skin compared to matched healthy controls. In addition, IL-13Rα1 expression on mast cells and eosinophils was significantly increased in L (P=0.034 and P=0.024, respectively) and NL (P=0.031 and P=0.046, respectively) AD skin compared to matched controls. Inhibition of the Type 1 receptor with anti-common γ chain antibody resulted in increased expression of MMP9 (P<0.001), which is a collagenase that is elevated in AD patients and may exacerbate inflammation-promoting tissue edema^3,4. Inhibition of the Type 2 receptor by eblasakimab induced suppression of genes including XBP1 (P<0.001), which is required for leptin-mediated Type 2 survival and cytokine production⁵, and CXCL8 (P=0.046), levels of which correlate with AD severity⁶.

Poster 2

Insight into novel itch pathways and spontaneous neuronal activity by targeting interleukin-13 receptor alpha 1 (IL-13Rα1) with eblasakimab 
(abstract ID: LB061)

Discussion

IL-4 and IL-13 have distinct effects on itch pathways and neuronal excitability that can be inhibited by targeting IL-13Rα1^7,8. Eblasakimab binds to the human Type 2 receptor subunit IL‑13Rα1 with high affinity, preventing signaling of IL‑4 and IL‑13 through the Type 2 receptor expressed on a range of immune and non‑immune cells, including sensory neurons^7,9. Sensitization of sensory neurons forms the cellular and molecular basis for multiple somatosensory disorders such as chronic itch, neurogenic inflammation, and forms of painful dysfunction¹⁰. The poster shows the results from a study to determine neuronal responses of human dorsal root ganglia (hDRG) neurons to itch signalling induced by pruritogens under various conditions. The effects of IL‑4 and IL‑13 on spontaneous neuronal activity (SA) in hDRG neurons induced by inflammatory soup (IS), which contains bradykinin and prostaglandin, were measured with and without eblasakimab as a model for hypersensitization of sensory neurons.

Results

Data presented in this poster confirm prior results of eblasakimab dampening neuronal sensitization caused by IL-4 and IL-13 on human neurons. In addition, IL-13 sensitized hDRG neurons to pro-adrenomedullin peptide 1-20 (PAMP20), demonstrating that the itch-specific MRGPRX2 receptor is expressed and functional in human sensory neurons, suggesting an enhancer role of Type 2 cytokines in a wide variety of itch-associated diseases. IL-4 induced spontaneous activity (SA) in hDRG neurons under inflammatory conditions, which was significantly reduced by eblasakimab. This may underly the mechanistic basis for altered neuronal sensitivity in inflammatory conditions. These data suggest that IL-13 and IL-4 may play distinct roles in affecting neuronal activity and eblasakimab was shown to block the effects of both cytokines.

The posters presented at the conference are available to access here.

References

1. Silverberg JI, et al. Ann Allergy Asthma Immunol. 2018 Sep;121(3):340-347.
2. Junttila IS., Front Immunol. 2018 Jun 7;9:888.
3. Devillers, A.C.A., et al. Clinical and Experimental Dermatology, 32: 311-313.
4. Jung, AR., et al. BMC Complement Altern Med 16, 416 (2016).
5. Zheng H, et al. Sci Rep. 2018 Jun 11;8(1):8905.
6. Amarbayasgalan T, et al. Int Arch Allergy Immunol.2013;160(1):63-74.
7. Oetjen L, et al. Cell. 2017;171(1):217‑228.
8. Miron Y, et al. J Allergy Clin Immunol. 2022:S0091‑6749(22)00233‑0.
9. Cevikbas F, et al. J Allergy Clin Immunol. 2014;133(2):448‑460.
10. Davidson S, et al. Pain. 2014; 155(9):1861‑1870.

About eblasakimab

Eblasakimab is a potential first-in-class monoclonal antibody targeting the IL-13 receptor, with the potential to deliver a differentiated safety and efficacy profile as well as an improved dosing regimen for atopic dermatitis patients. In September 2021, ASLAN announced positive results from the Phase 1b multiple-ascending-dose study that established proof-of-concept of ASLAN004 and supported its potential as a novel treatment for AD. In January 2022, ASLAN initiated the TREK-AD Phase 2b trial to evaluate the safety and efficacy of eblasakimab in moderate-to-severe AD patients. Topline data is expected in the first half of 2023. The TREK-DX trial evaluating the efficacy and safety of eblasakimab in adult patients with moderate-to-severe AD who have previously been treated with dupilumab is expected to enroll the first patient in the fourth quarter of 2022.

About ASLAN Pharmaceuticals

ASLAN Pharmaceuticals (Nasdaq: ASLN) is a clinical-stage, immunology-focused biopharmaceutical company developing innovative treatments to transform the lives of patients. ASLAN is currently evaluating eblasakimab, a potential first-in-class antibody targeting the IL-13 receptor, in atopic dermatitis, and farudodstat, a potent oral inhibitor of the enzyme DHODH, in autoimmune disease. ASLAN has a team in California and in Singapore. For additional information please visit www.aslanpharma.com or follow ASLAN on LinkedIn.

Forward looking statements

This release contains forward-looking statements. These statements are based on the current beliefs and expectations of the management of ASLAN Pharmaceuticals Limited and/or its affiliates (the "Company"). These forward-looking statements may include, but are not limited to, statements regarding the Company’s business strategy and clinical development plans; the Company’s plans to develop and commercialize eblasakimab; the safety and efficacy of eblasakimab; the Company’s plans and expected timing with respect to clinical trials, clinical trial enrolment and clinical trial results for eblasakimab; and the potential of eblasakimab as a first-in-class treatment for atopic dermatitis. The Company’s estimates, projections and other forward-looking statements are based on management's current assumptions and expectations of future events and trends, which affect or may affect the Company’s business, strategy, operations, or financial performance, and inherently involve significant known and unknown risks and uncertainties. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of many risks and uncertainties, which include, unexpected safety or efficacy data observed during preclinical or clinical studies; clinical site activation rates or clinical trial enrolment rates that are lower than expected; the impact of the COVID-19 pandemic or the ongoing conflict between Ukraine and Russia on the Company’s business and the global economy; general market conditions; changes in the competitive landscape; and the Company’s ability to obtain sufficient financing to fund its strategic and clinical development plans. Other factors that may cause actual results to differ from those expressed or implied in such forward-looking statements are described in the Company’s US Securities and Exchange Commission filings and reports (Commission File No. 001- 38475), including the Company’s Annual Report on Form 20-F filed with the US Securities and Exchange Commission on March 25, 2022. All statements other than statements of historical fact are forward-looking statements. The words “believe,” “may,” “might,” “could,” “will,” “aim,” “estimate,” “continue,” “anticipate,” “intend,” “expect,” “plan,” or the negative of those terms, and similar expressions that convey uncertainty of future events or outcomes are intended to identify estimates, projections, and other forward-looking statements. Estimates, projections, and other forward-looking statements speak only as of the date they were made, and, except to the extent required by law, the Company undertakes no obligation to update or review any estimate, projection, or forward-looking statement.

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